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By Annette Bak, Margaret Landis, John S. Morrison, and Mehran Yazdanian

Annette BakMeg LandisJohn MorrisonMehran Yazdanian




A chemical cannot be a drug, no matter how active nor how specific its action, unless it is also taken appropriately into the body (absorption), distributed to the right parts of the body, metabolized in a way that does not instantly remove its activity, and eliminated in a suitable manner—a drug must get in, move about, hang around, and then get out.

ADMET—Turning Chemicals into Drugs, John Hodgson, 2001

A recent review of phase 2 clinical study failures from 2008 to 2010 showed that efficacy was the major cause of attrition in the pharmaceutical industry’s drug pipelines (51 percent), followed by strategic reasons (29 percent) and safety considerations (19 percent). The attrition rates based on efficacy and safety are often related to suboptimal pharmacokinetics and pharmaceutical properties. Therefore the question “How is a drug candidate selected for development from among many potential discovery compounds?” is a very important one; choosing a suitable candidate to enter the prolonged and costly development process requires assessing the properties of multiple candidates and weighing the overall benefits and liabilities of each. The key properties include target efficacy, pharmacokinetic (PK) profile, physicochemical and biopharmaceutical characteristics, as well as any safety liabilities.

Input and interaction from the scientific disciplines of chemistry, biology, drug metabolism and pharmacokinetics, pharmaceutics, toxicology, and analytical development are therefore required to assess the potential of candidates for drug development. “Developability” assessment can be defined as an integrated assessment aided by studies that determine key physicochemical, biopharmaceutical, PK, metabolic, and safety properties of a new chemical entity (NCE) that help in distinguishing “lead compounds” from “development candidates.” Thus “developability” assessment represents an exciting and dynamic field in the pharmaceutical sciences, one that is rapidly developing novel in silico, in vitro, and in vivo techniques and tools for improving both the efficiency and effectiveness of the drug candidate selection process. The ultimate goal of a “developability” assessment is to select a drug candidate for development with appropriate pharmaceutical properties to allow it to reach a biological target, carry out a biochemical function, and achieve a pharmacodynamic result with minimal off-target interactions.

We overview developability assessments in the July issue of the AAPS Newsmagazine. Read How Are Drug Development Candidates Selected?, from the Drug Discovery and Development Interface (DDDI) section, and then participate in the discussion point below.

What do you think of the current state of drug developability assessment? Has the use of such developability assessments reduced the need for developing nonconventional and costly drug delivery approaches? What more predictive capabilities, technologies, analyses, inputs, innovations are needed?

Annette Bak, Ph.D., is the NJ Pharmaceutical Sciences Discovery lead for Merck Research Laboratories. She received her degree in pharmaceutical chemistry from the University of Copenhagen and completed a postdoctoral fellowship at the University of Kansas. Margaret Landis, Ph.D., is an associate research fellow in the early discovery and development formulation group at Pfizer, Inc. She received her doctorate in organic chemistry from Columbia University. John S. Morrison, Ph.D., a senior research investigator with the Pharmaceutical Candidate Optimization group of Bristol-Myers Squibb engaged in drug candidate selection and preclinical support. He received his doctorate in physical organic chemistry from the University of Western Ontario. Mehran Yazdanian, Ph.D., is the senior director of analytical development and validation at Teva Branded Pharmaceutical Products R&D Inc. He received his degree in pharmaceutics from the University of Wisconsin-Madison and has been involved for drug discovery support for the past two decades.